Aminophylline exposure alters mouse bone marrow-derived mast cell adenosine responsiveness

Aminophylline-treated mouse bone marrow-derived mast cells exhibit a hyperresponsiveness to adenosine addition (10(-6) to 10(-4) mol/L) at the time of secretagogue challenge coincident with an up regulation of adenosine receptor numbers. This effect on beta-hexosaminidase release is maximal at 100 mumol/L of aminophylline, evident after 5 days of aminophylline exposure, and reversed by 6 days after washing. Neither radiolabeled arachidonic acid nor leukotriene C4 release in the absence or presence of adenosine was altered by aminophylline treatment. Although cAMP levels were dynamically changed by adenosine or secretagogue, these changes were not different in the two cell populations; resting and challenged mast cell adenosine levels were similarly unaffected by aminophylline. The long-term action of aminophylline on mouse bone marrow-derived mast cells appears to be primarily on adenosine receptors and thereby on preformed mediators, and this action may have some importance in the pathophysiology and treatment of asthma.